iScience, Journal Year: 2024, Volume and Issue: 27(11), P. 111163 - 111163
Published: Oct. 11, 2024
Language: Английский
Diagnostics, Journal Year: 2025, Volume and Issue: 15(8), P. 945 - 945
Published: April 8, 2025
Progressive Supranuclear Palsy (PSP) is an atypical Parkinsonism, pathologically described as a four-repeat tauopathy. The contemporary criteria for diagnosis of PSP indicate akinesia, oculomotor dysfunction, postural instability, and language/cognitive impairment core symptoms. Among these features, the first two are linked to PSP—Parkinsonism predominant (PSP-P). PSP-P second most common subtype PSP, following PSP—Richardson’s syndrome (PSP-RS), associated with more gradual deterioration, beneficial course, longer life expectancy after diagnosis. It also problematic in terms clinical evaluation, this entity may overlap Parkinson’s disease (PD) early stages other Parkinsonisms advanced stages. evolution understanding possible progress care therapy leads necessity finding optimal examination methods sufficient sensitivity specificity. In context, seems crucial point. goal narrative review provide overview possibilities provided by Magnetic Resonance Imaging (MRI) assessments analyze their strengths weaknesses.
Language: Английский
Citations
0
Genome Medicine, Journal Year: 2025, Volume and Issue: 17(1)
Published: March 4, 2025
Alzheimer's disease (AD) is a complex neurodegenerative disorder with substantial genetic influence. While genome-wide association studies (GWAS) have identified numerous risk loci for late-onset AD (LOAD), the functional mechanisms underlying most of these associations remain unresolved. Large genomic rearrangements, known as structural variants (SVs), represent promising avenue elucidating such within some loci. By leveraging data from two ongoing cohort aging and dementia, Religious Orders Study Rush Memory Aging Project (ROS/MAP), we performed analysis testing 20,205 common SVs 1088 participants whole genome sequencing (WGS) data. A range other age-related clinical neuropathologic traits were examined. First, mapped across 81 discovered 22 in linkage disequilibrium (LD) GWAS lead directly associated phenotypes tested. The strongest was deletion an Alu element 3'UTR TMEM106B gene, high LD respective locus multiple AD-related disorders (ADRD) phenotypes, including tangles density, TDP-43, cognitive resilience. this also linked to lower protein abundance. We found 22-kb depression ROS/MAP bearing similar patterns SNPs at IQCK locus. In addition, leveraged our catalog SV-GWAS replicate characterize independent findings SV-based five diseases. Among findings, highlight replication significant progressive supranuclear palsy (PSP), markers 17q21.31 MAPT inversion 1483-bp CYP2A13 locus, along suggestive associations, 994-bp duplication LMNTD1 suggestively 3958-bp DOCK5 Lewy body (LBD) (P = 3.36 × 10-4). still limited sample size, study highlights utility provides valuable resource characterization effects pathogenesis.
Language: Английский
Citations
0
Movement Disorders, Journal Year: 2025, Volume and Issue: unknown
Published: March 8, 2025
The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents strongest risk locus in progressive supranuclear palsy (PSP). To investigate association between CNVs on 17q.21.31 of PSP. Utilizing whole genome sequencing data from 1684 PSP cases 2392 controls, (α, β, γ) within were identified analyzed for their We found that γ was associated increased (odds ratio [OR] = 1.10, P 0.0018). From H1β1γ1 (OR 1.21) H1β2γ1 1.24) to H1β1γ4 1.57), H1 additional copies displayed a higher frequency sub-haplotype H1c rises 1% individuals two 88% those eight copies. Additionally, duplication up-regulates expression ARL17B, LRRC37A/LRRC37A2, NSFP1, while down-regulating KANSL1. Single-nucleus RNA-seq dorsolateral prefrontal cortex analysis reveals primarily LRRC37A/LRRC37A2 neuronal cells. is after adjusting H1/H2, indicating complex structure at an important consideration when evaluating genetic © 2025 Author(s). Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society.
Language: Английский
Citations
0
Immunobiology, Journal Year: 2025, Volume and Issue: unknown, P. 152892 - 152892
Published: March 1, 2025
Progressive supranuclear palsy (PSP) is a neurodegenerative disease showing pathological tau accumulation in subcortical neurons and glial cells. The human leukocyte antigen (HLA) locus on chromosome 6 polymorphic region with complex linkage patterns that has been implicated several autoimmune neurological disorders. HLA not systematically examined PSP. It unclear whether can interact to induce an mechanism. We evaluated autopsy confirmed PSP cohort (n = 44) compared allele/haplotype frequencies those of the reference group local deceased Canadian donor pool. performed HLA-Tau peptide binding prediction modelling Class II - Tau Peptide interactions. Odds ratio was 2.94 (95 % CI 1.01 8.55; p 0.047) for DQB1*06:01 allele, 2.59 1.39 4.83; 0.0025) narcolepsy-associated haplotype (DRB1*15:01-DQB1*06:02). One patient 4-repeat PSP-type pathology carrier IgLON5-associated (DRB1*10:01-DQB1*05:01). interactions revealed strong-binding peptides but PSP-protofilament fold alleles DQA1*01:02-DQB1*06:02 DQA1*01:03-DQB1*06:01. Our study suggests epitopes within may bind are found subset patients supporting notion pathophysiological component. These findings have implications subtyping stratifying therapies, including targeting immune modulation.
Language: Английский
Citations
0
Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)
Published: Oct. 14, 2024
Language: Английский
Citations
1
Immunological Reviews, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 24, 2024
Summary Alzheimer's disease (AD) is a progressive neurological disorder and the most common cause of dementia. Genetic analyses identified apolipoprotein E ( APOE ) as strongest genetic risk for late‐onset AD. Studies have shown that ApoE modulates AD pathogenesis in part by influencing amyloid‐β (Aβ) deposition. However, also appears to regulate elements via regulation innate immune response, especially through microglial astrocyte activation. In model systems, it regulates changes T‐cells. This review focuses on key findings advanced our understanding role current view response regulated AD, while discussing open questions areas future research.
Language: Английский
Citations
1
medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 27, 2024
The chromosome 17q21.31 region, containing a 900 Kb inversion that defines H1 and H2 haplotypes, represents the strongest genetic risk locus in progressive supranuclear palsy (PSP). In addition to H2, various structural forms of 17q21.31, characterized by copy number α, β, γ duplications, have been identified. However, specific effect each form on PSP has never evaluated large cohort study.
Language: Английский
Citations
0
iScience, Journal Year: 2024, Volume and Issue: 27(11), P. 111163 - 111163
Published: Oct. 11, 2024
Language: Английский
Citations
0